A molecular clone derived from simian immunodeficiency virus (SIV/Mne)- infected HuT 78 cells has been completely sequenced and shown to be 82% identical to HIV-2. This clone expresses all the structural and regulatory genes of SIV and is infectious and pathogenic. Two pig-tailed macaques (M. nemestrina) infected with this clone experienced marked CD4+ depletion; one died 83 weeks after infection. These animals provide a model for following changes in the SIV envelope (env) gene as a function of time after infection. Two regions of env, within the variable regions Vl and V4, showed change in up to 40% of their amino acids when AIDS became apparent. The region of SIV env that corresponds to the immunodominant V3 loop of HIV was conserved. Overall, the rate of change in env was approximately l%/year at the amino acid level, which is 10 to the sixth power-fold faster than the rate of mutation in cellular DNA. Analysis of the biological properties of these variant envelope proteins will be useful in defining the mechanisms underlying progression to AIDS. Transmission of HIV from an infected pregnant woman to her infant is the most important mechanism of HIV infection in children. The mode of transmission of HIV from mother to fetus, the time of infection, and the mechanism(s) that protects approximately two-thirds of infants born to HIV-infected mothers are unknown. To facilitate a systematic study of maternal-fetal transmission, we have developed a nonhuman primate model by infecting pregnant M. nemestrina with a pathogenic, uncloned strain of SIV/Mne. Three animals infected during the third trimester delivered healthy infants. One of the three infants, a male born 31 days after his mother was infected, became virus-positive but failed to produce SIV-specific antibody. He died with overt AIDS and disseminated adenovirus infection at 6 months of age. This is the first reported maternal-fetal transmission with SIV and will serve as a useful model for determining factors influencing the frequency of transmission as well as for studies of the effectiveness of antiviral therapy.